Diffuse Alveolar Hemorrhage (DAH)


Epidemiology


Etiology

Capillaritis

Rheumatologic Disease-Associated Capillaritis

Systemic Vasculitis-Associated Capillaritis

Drug-Associated Capillaritis

Other Capillaritis

  • Acute Lung Transplant Rejection (see Acute Lung Transplant Rejection)
  • Acute Antibody-Mediated Lung Transplant Rejection (see Acute Antibody-Mediated Lung Transplant Rejection)
    • Physiology
      • Capillaritis is Often Present
  • Hematopoietic Stem Cell Transplant (HSCT) (see Hematopoietic Stem Cell Transplant)
    • Epidemiology
      • Rare
    • Mechanisms
      • Hemoptysis May Be Due to Diffuse Alveolar Hemorrhage (as an Early Complication of HSCT)
      • Hemoptysis May Be Due to Idiopathic Pneumonia Syndrome (as a Late Complication of HSCT): idiopathic pneumonia syndrome is due to diffuse lung injury (from a combination of drugs, radiation, and/or thrombocytopenia) (Am J Respir Crit Care Med, 2011) [MEDLINE]
      • Underlying Viral/Fungal Infection Can Also Contribute to Diffuse Alveolar Hemorrhage or Idiopathic Pneumonia Syndrome
    • Prognosis
      • May Be Fatal
  • Infective Endocarditis (see Endocarditis)
  • Leptospirosis (see Leptospirosis)
    • Physiology
      • Reported Cases Demonstrate Leptospiral Antigen within Macrophages in the Septa and Alveoli (Rev Soc Bras Med Trop, 2002) [MEDLINE]
      • Clinical
        • Life-Threatening Hemoptysis May Occur
  • Ulcerative Colitis (UC) (see Ulcerative Colitis)

Bland Alveolar Hemorrhage

Diffuse Alveolar Damage (DAD)

  • Acute Interstitial Pneumonia (AIP) (see Acute Interstitial Pneumonia)
    • Epidemiology
      • XXXX
  • Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)
    • General Comments
      • Diffuse Alveolar Damage is the Most Common Pathologic Finding in Acute Respiratory Distress Syndrome (ARDS)
    • Infection
      • Aspiration Pneumonia (see Aspiration Pneumonia)
      • Bacterial Pneumonia
      • Fungal Pneumonia (Pneumocystis Jirovecii, etc)
      • Viral Pneumonia (Influenza Virus, SARS-CoV2, etc)
    • Massive Transfusion
    • Sepsis (see Sepsis)
    • Trauma
    • Drug/Toxin
      • Amiodarone (Cordarone) (see Amiodarone)
      • Amphetamine (see Amphetamine)
      • Azathioprine (Imuran) (see Azathioprine): diffuse alveolar damage may occur (Am J Clin Pathol, 1984) [MEDLINE]
      • Crack Cocaine (see Cocaine)
        • Epidemiology
        • Hemoptysis (and Diffuse Alveolar Hemorrhage) Has Been Described in 6% of Habitual Free-Base (Crack) Cocaine Smokers
        • Levamisole-Contaminated Cocaine Has Been Associated with Pulmonary Hemorrhage in Several Case Reports
      • Electronic Cigarrettes/Vaping (see xxxx) (NEJM, 2020) [MEDLINE]
        • Clinical
        • E-Cigarette Use/Vaping Has Been Associated with ARDS/Diffuse Alveolar Damage, with Hemoptysis Present in 11% of Cases at Time of Presentation (NEJM, 2020) [MEDLINE
        • Vaping Has Also Been Associated with Acute Eosinophilic Pneumonia, Organizing Pneumonia, Lipoid Pneumonia, Hypersensitivity Pneumonitis, and Giant Cell Interstitial Pneumonitis
      • Fludarabine (Fludara) (see Fludarabine): DAH may occur (Haematologica, 2000) [MEDLINE], as well as diffuse alveolar damage (Chest, 2002) [MEDLINE]
      • Isocyanates (see xxxx)
      • Mitomycin (see Mitomycin): diffuse alveolar damage may occur (Cancer, 1980) [MEDLINE]
      • Nitrofurantoin (Macrodantin) (see Nitrofurantoin)
      • NItrogen Dioxide (see NItrogen Dioxide): diffuse alveolar damage may occur (J Intern Med, 1996) [MEDLINE] (MMWR Morb Mortal Wkly Rep, 2012) [MEDLINE] (Lung, 2007) [MEDLINE]
        • Exposures
        • Indoor Ice Arenas (Due to Propane-Powered Ice Surfacing Equipment with Inadequate Ventilation)
        • Silo Fillers
      • Penicillamine (see Penicillamine)
      • Propylthiouracil (PTU) (see Propylthiouracil)
      • Sirolimus (XXXXXXX) (see Sirolimus)
      • Trimellitic Anhydride (see Trimellitic Anhydride)
  • Connective Tissue Disease
  • Cryptogenic Organizing Pneumonia (COP) (see Cryptogenic Organizing Pneumonia)
  • High-Altitude Pulmonary Edema (HAPE) (see High-Altitude Pulmonary Edema)
  • Idiopathic Pulmonary Fibrosis (IPF) (see Idiopathic Pulmonary Fibrosis)
  • Radiation Therapy/Radiation Pneumonitis (see Radiation Therapy and Radiation Pneumonitis and Fibrosis)
  • Toxic Inhalation

Other


Diagnosis

Complete Blood Count (CBC) (see Complete Blood Count)

Serum Chemistry

  • Elevated Creatinine: may be seen in cases with renal involvement

Arterial Blood Gas (ABG) (see Arterial Blood Gas)

Chest X-Ray (see Chest X-Ray)

  • xxx

Chest CT (see Chest Computed Tomography)

  • Findings
    • Alveolar Filling/Consolidation
    • Ground Glass Infiltrates
    • Interstitial Fibrosis: seen in chronic/Recurrent cases
  • Example: diffuse alveolar hemorrhage in a patient with Wegener’s granulomatosis -> note the ground glass infiltrates in the right lung and extensive alveolar filling in the left lung (alveolar hemorrhage was confirmed in the left lower lobe by bronchoscopy)
WEG DAH

Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests)

  • Restriction
  • DLCO
    • Increased During Acute Diffuse Alveolar Hemorrhage: resolves within 48-72 hrs (as hemoglobin is degraded to hemosiderin)

Anti-Neutrophil Cytoplasmic Antibody (ANCA) (see Anti-Neutrophil Cytoplasmic Antibody)

  • p-ANCA: much less specific than c-ANCA titers
    • p-ANCA: can be positive in microscopic polyangiitis, Churg-Strauss, pauci-immune glomerulonephritis, some cases of isolated pulm capillaritis, polyarteritis nodosa, and ulcerative colitis

Bronchoscopy (see Bronchoscopy)

  • Bronchoalveolar Lavage (BAL): necessary to rule out infection and other etiologies of alveolar infiltrates
    • Increasingly Serial Bloody BAL Fluid is Diagnostic
    • Cell Count and Differential:: presence of hemosiderin-laden macrophages suggests chronic hemorrhage (rather than biopsy-related bleeding)
      • Quantitative Scoring of Alveolar Macrophage Hemosiderin Concentration: sensitive for diagnosis of DAH

Video-Assisted Thoracoscopic Surgery (VATS) with Lung Biopsy (see Video-Assisted Thoracoscopic Surgery and Open Lung Biopsy)

  • May Be Used in Cases with Equivocal Serology: but is usually not necessary

Renal Biopsy (see Renal Biopsy)

  • May Be Positive: even in the absence of overt renal involvement

Clinical Manifestations

Duration of Symptoms

  • Symptoms are Usually Present for Period of Days-Weeks

Pulmonary Manifestations

Acute Respiratory Failure (see Respiratory Failure)

  • Epidemiology
    • May Occur in Severe Cases

Alveoar Infiltrates/Pneumonia-Like Presentation

Diffuse Pulmonary Ossification (DPO) (see Diffuse Pulmonary Ossification)

  • Epidemiology
    • Diffuse Alveolar Hemorrhage Has Been Reported to Precede Diffuse Pulmonary Ossification in Some Cases

Hemoptysis (see Hemoptysis)

  • Epidemiology
    • Common

Interstitial Pulmonary Fibrosis (see Interstitial Lung Disease)

  • Epidemiology
    • Occurs with Recurrent Diffuse Alveolar Hemorrhage

Treatment

Management of Post-Stem Cell Transplant Diffuse Alveolar Hemorrhage

  • Corticosteroids (see Corticosteroids)
    • Methylprednisolone (Solumedrol) (see Methylprednisolone): 125-250 mg q6 hrs x 4-6 days, then taper over 2 wks) improve resp status and survival

References

Etiology